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Chronic Lymphocytic Leukemia (CLL)

This is the most common variety of leukaemia, occurs in elderly person. CLL constitutes 25% of all leukaemia. Transformation into ALL is not a feature
Clinical Features (Mostly asymptomatic)
Weight loss stage, infection, bleeding, enlarged rubbery nontender nodes, hepatosplenomegaly.
Stages of CLL
Stage       Feature
0              Increase TLC
1              Lymphadenopathy
2              Splenomegaly      
3              Anemia
4              Thrombocytopenia

Investigations diagnosis on routine blood test
  1. Mild anemia: Coombs’ positive hemolytic anemia it occurs due to warm antibody present in CLL.
  2. WBC count: 50,000 to 200,000/ml. The cells are small B cell lymphocytes (Absolute lymphocytosis). 
  3. Platelet count is, normal or reduced.
  4. Total proteins and immunoglobulin levels are low as B lymphocytes fail to produce antibodies.
Genetic abnormality
  1. Deletion on long arm of chromosome 13 (13q - 14):  = Good prognosis
  2. Chromosome 11 deletion (11q, 22-23 deletion), = bulky Lymphadenopathy = Poor prognosis
  3. Chromosome 17 deletion (17 P 21 deletion) = Poor prognosis
  4. Chromosome 12 trisomy (trisomy 12) = Intermediate prognosis
Extra Edge:
The interphase cytogenetics by FISH can accurately detect chromosomal abnormalities in more than 80% of all cases.
CLL = CD5 + CD19 +, CD23 + (Co expression of CD5 + CD19).

CLL whose cell of origin has the mutated IgVH : Good prognosis
CLL whose cell of origin has the un-mutated IgVH : Poor prognosis


Prognostic factors
IgVH = mutation in variable reason of heavy chain. 

Table - Staging of Typical B Cell Lymphoid Leukemia
Stage Clinical Features Median Survival, Years
RAI System
0: Low risk Lymphocytosis only in blood and marrow >10
I: Intermediate risk Lymphocytosis + lymphadenopathy + splenomegaly ± hepatomegaly 7
III: High risk Lymphocytosis + anemia 1.5
IV Lymphocytosis + thrombocytopenia  
Binet System
A Fewer than three areas of clinical lymphadenopathy; no anemia or thrombocytopenia >10
B Three or more involved node areas; no anemia or thrombocytopenia 7
C Hemoglobin 10 g/dL and/or platelets <100,000/mL 2

Pathology:  M/E pseudofollicular pattern with proliferative centre.
Rituximab is also effective in the treatment of lymphoma and rheumatoid arthritis. It is a anti CD-20 drug. (AIIMS May 2008)

Rx: Chlorambucil
Newer Drugs
  1. Fludarabine
  2. Rituximab (AIIMS May 2008)
  3. Alemtuzumab
Recent Advances - New Drug
Alemtuzumab is a monoclonal antibody. It is used in treatment of B-cell CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. It is also effective in CD-52 expressing lymphoid tumor. 

Recent Advances – New Drugs
  1. Trastuzumab – CA breast                          
  2. Cetuximab – Ca colon, Squamous cell carcinoma of Head and Neck.
  3. Panitumumab -  Ca colon                              
  4. Bevacizumab – Cancer of Lung, colon breast.

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